Nrf2在缺血性脑损伤中的关键性作用

The key role of Nrf2 in ischemic stroke

缺血性脑卒中是全球范围内致死及致残的主要原因之一。核因子E2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)是一种调节机体氧化还原反应平衡的蛋白质分子,通过协调多种细胞保护基因,参与抵抗内源性或外源性压力。Nrf2信号通路不仅严格调控机体氧化还原稳态,同时还参与调节机体代谢的多个过程。因此,靶向Nrf2已成为预防和治疗包括缺血性脑卒中在内的中枢神经系统疾病的潜在策略。首先介绍Nrf2和Kelch样ECH相关蛋白1(Kelch-like ECH-associated protein 1,Keap1)的结构特征,并简要描述Nrf2通路的激活和调控过程。然后讨论Nrf2通路的病理生理机制、上游调节剂和下游靶点。在此背景下,扩展到Nrf2在缺血性脑卒中后的作用,并探讨潜在的治疗方向。

Ischemic stroke is one of the main causes of death and disability worldwide.Nuclear factor E2-related factor 2(Nrf2)is an important transcription factor that regulates the balance of the body's redox reaction.It participates in resisting endogenous or exogenous stress by coordinating a variety of cytoprotective genes.The Nrf2 signaling pathway not only strictly regulates the body's redox homeostasis,but also participates in the regulation of multiple processes in the body metabolism.Therefore,targeting Nrf2 has become a potential strategy for the prevention and treatment of central nervous system diseases including ischemic stroke.In this review,we first introduced the structural features of Nrf2 and Kelch-like ECH-related protein 1(Keap1),and briefly described the activation and regulation of the Nrf2 pathway.Next,we discussed the pathological and physiological mechanism,upstream regulators and downstream targets of the Nrf2 pathway.In this context,we extended the discussion to the role of Nrf2 after ischemic stroke and explored potential therapeutic directions.